1,858 research outputs found
The Frames Behind the Games: Player's Perceptions of Prisoner's Dilemma, Chicken, Dictator, and Ultimatum Games
The tension between cooperative and competitive impulses is an eternal issue for every society. But how is this problem perceived by individual participants in the context of a behavioral games experiment? We first assess individual differences in playersâ propensity to cooperate in a series of experimental games. We then use openended interviews with a subset of those players to investigate the various concepts (or âframesâ) they used when thinking about self-interested and cooperative actions. More generally, we hope to raise awareness of playerâs perceptions of experimental environments to inform both the design and interpretation of experiments and experimental data.Laboratory Experiment, Frames, Selfishness, Cooperation
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Lifespan-increasing drug nordihydroguaiaretic acid inhibits p300 and activates autophagy.
Aging is characterized by the progressive loss of physiological function in all organisms. Remarkably, the aging process can be modulated by environmental modifications, including diet and small molecules. The natural compound nordihydroguaiaretic acid (NDGA) robustly increases lifespan in flies and mice, but its mechanism of action remains unclear. Here, we report that NDGA is an inhibitor of the epigenetic regulator p300. We find that NDGA inhibits p300 acetyltransferase activity in vitro and suppresses acetylation of a key p300 target in histones (i.e., H3K27) in cells. We use the cellular thermal shift assay to uniquely demonstrate NDGA binding to p300 in cells. Finally, in agreement with recent findings indicating that p300 is a potent blocker of autophagy, we show that NDGA treatment induces autophagy. These findings identify p300 as a target of NDGA and provide mechanistic insight into its role in longevity
Age- and stress-associated C. elegans granulins impair lysosomal function and induce a compensatory HLH-30/TFEB transcriptional response.
The progressive failure of protein homeostasis is a hallmark of aging and a common feature in neurodegenerative disease. As the enzymes executing the final stages of autophagy, lysosomal proteases are key contributors to the maintenance of protein homeostasis with age. We previously reported that expression of granulin peptides, the cleavage products of the neurodegenerative disease protein progranulin, enhance the accumulation and toxicity of TAR DNA binding protein 43 (TDP-43) in Caenorhabditis elegans (C. elegans). In this study we show that C. elegans granulins are produced in an age- and stress-dependent manner. Granulins localize to the endolysosomal compartment where they impair lysosomal protease expression and activity. Consequently, protein homeostasis is disrupted, promoting the nuclear translocation of the lysosomal transcription factor HLH-30/TFEB, and prompting cells to activate a compensatory transcriptional program. The three C. elegans granulin peptides exhibited distinct but overlapping functional effects in our assays, which may be due to amino acid composition that results in distinct electrostatic and hydrophobicity profiles. Our results support a model in which granulin production modulates a critical transition between the normal, physiological regulation of protease activity and the impairment of lysosomal function that can occur with age and disease
Attributable costs of surgical site infection and endometritis after low transverse cesarean delivery
BACKGROUND: Accurate data on costs attributable to hospital-acquired infections are needed in order to determine their economic impact and the cost-benefit of potential preventive strategies. OBJECTIVE: Determine the attributable costs of surgical site infection (SSI) and endometritis (EMM) after cesarean section using two different methods. DESIGN: Retrospective cohort. SETTING: Barnes-Jewish Hospital, a 1250-bed academic tertiary care hospital. PATIENTS: 1,605 women who underwent low transverse cesarean section from 7/1999 â 6/2001. METHODS: Attributable costs of SSI and EMM were determined by generalized least squares (GLS) and propensity score matched-pairs using administrative claims data to define underlying comorbidities and procedures. For the matched-pairs analyses, uninfected control patients were matched to patients with SSI or with EMM based on their propensity to develop infection, and the median difference in costs calculated. RESULTS: The attributable total hospital cost of SSI calculated by GLS was 2,852. The attributable total hospital cost of EMM calculated by GLS was 3,842. The majority of excess costs were associated with room and board and pharmacy costs. CONCLUSIONS: The costs of SSI and EMM were lower than SSI costs reported after more extensive operations. The attributable costs of EMM calculated using the two methods were very similar, while the costs of SSI calculated using propensity score matched-pairs were lower than the costs calculated by GLS. The difference in costs determined by the two methods needs to be considered by investigators performing cost analyses of hospital-acquired infections
Development and validation of a Clostridium difficile infection risk prediction model
OBJECTIVE: The purpose of this study was to develop and validate a risk prediction model that could identify patients at high risk for Clostridium difficile infection (CDI) before they develop disease. DESIGN: Retrospective cohort. SETTING: Tertiary care medical center. PATIENTS: Patients admitted to the hospital for â„48 hours from 1-1-2003 through 12-31-2003. METHODS: Data were collected electronically from the hospitalâs Medical Informatics database and analyzed with logistic regression to determine variables that best predicted patientsâ risk for development of CDI. Model discrimination and calibration were calculated. The model was bootstrapped 500 times to validate the predictive accuracy. A receiver operating characteristic (ROC) curve was calculated to evaluate potential risk cut-offs. RESULTS: 35,350 admissions with 329 CDI cases were included. Variables in the risk prediction model were age, CDI pressure, admissions in previous 60 days, modified Acute Physiology Score, days on high risk antibiotics, low albumin, admission to an ICU, and receipt of laxatives, gastric acid suppressors, or antimotility drugs. The calibration and discrimination of the model were very good to excellent (C index=0.88; Brier score 0.009). CONCLUSIONS: The CDI risk prediction model performed well. Further study is needed to determine if it could be used in a clinical setting to prevent CDI-associated outcomes and reduce costs
The Effects of Accentuated Eccentric Loading on Barbell and Trap Bar Countermovement Jumps
This study examined effects of accentuated eccentric loading (AEL) on barbell and trap bar loaded countermovement jumps (LCMJ). Twenty-one subjects (16 male, 5 female; Age: 23.5 ± 1.8 years; Body mass: 81.4 ± 10.6 kg; Height: 176.9 ± 7.2 cm; Training age: 7.1 ± 2.6 years) participated in this study. Upon establishing one repetition maximum and baseline jumping conditions, three experimental loading sessions were completed in random order. Barbell and trap bar LCMJ were performed with a spectrum of fixed loads from 20-50 kg during control conditions and with additional AEL loads of 10, 20, or 30 kg for experimental conditions. According to coefficients of variation
Use of short-tandem repeat (STR) fingerprinting to validate sample origins in hepatitis C virus molecular epidemiology studies
Sequence analysis is used to define the molecular epidemiology and evolution of the hepatitis C virus. Whilst most studies have shown that individual patients harbour viruses that are derived from a limited number of highly related strains, some recent reports have shown that some patients can be co-infected with very distinct variants whose frequency can fluctuate greatly. Whilst co-infection with highly divergent strains is possible, an alternative explanation is that such data represent contamination or sample mix-up. In this study, we have shown that DNA fingerprinting techniques can accurately assess sample provenance and differentiate between samples that are truly exhibiting mixed infection from those that harbour distinct virus populations due to sample mix-up. We have argued that this approach should be adopted routinely in virus sequence analyses to validate sample provenance
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